21-38299525-C-T

Variant names:

• chr21-38299525-C-T
• rs3746876
• NM_170736.3:c.264C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_170736.3(KCNJ15):​c.264C>T​(p.Ile88Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,614,088 control chromosomes in the GnomAD database, including 478 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.031 (176 hom., cov: 32)
  • Exomes 𝑓: 0.011 (302 hom.)
• Consequence: KCNJ15 NM_170736.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 14 publications found

Genes affected

KCNJ15 (HGNC:6261): (potassium inwardly rectifying channel subfamily J member 15) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Eight transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2013]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-1.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.081 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170736.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ15	NM_170736.3	MANE Select	c.264C>T	p.Ile88Ile	synonymous	Exon 3 of 3	NP_733932.1	Q99712
	KCNJ15	NM_001276435.2		c.264C>T	p.Ile88Ile	synonymous	Exon 5 of 5	NP_001263364.1	Q99712
	KCNJ15	NM_001276436.2		c.264C>T	p.Ile88Ile	synonymous	Exon 5 of 5	NP_001263365.1	Q99712

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ15	ENST00000398938.7	TSL:1 MANE Select	c.264C>T	p.Ile88Ile	synonymous	Exon 3 of 3	ENSP00000381911.2	Q99712
	KCNJ15	ENST00000328656.8	TSL:1	c.264C>T	p.Ile88Ile	synonymous	Exon 4 of 4	ENSP00000331698.3	Q99712
	KCNJ15	ENST00000398930.5	TSL:5	c.264C>T	p.Ile88Ile	synonymous	Exon 4 of 4	ENSP00000381904.1	Q99712

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4751 AN: 152086 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0876

Gnomad SAS AF: 0.00353

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00745

Gnomad OTH AF: 0.0263

GnomAD2 exomes AF: 0.0199 AC: 5001 AN: 251476 AF XY: 0.0176

Gnomad AFR exome AF: 0.0837

Gnomad AMR exome AF: 0.0101

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.0966

Gnomad FIN exome AF: 0.0170

Gnomad NFE exome AF: 0.00764

Gnomad OTH exome AF: 0.0125

GnomAD4 exome AF: 0.0114 AC: 16719 AN: 1461884 Hom.: 302 Cov.: 32 AF XY: 0.0108 AC XY: 7826 AN XY: 727246

African (AFR) AF: 0.0826 AC: 2767 AN: 33480

American (AMR) AF: 0.0106 AC: 474 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00333 AC: 87 AN: 26136

East Asian (EAS) AF: 0.0667 AC: 2649 AN: 39700

South Asian (SAS) AF: 0.00589 AC: 508 AN: 86256

European-Finnish (FIN) AF: 0.0148 AC: 792 AN: 53418

Middle Eastern (MID) AF: 0.0114 AC: 66 AN: 5768

European-Non Finnish (NFE) AF: 0.00747 AC: 8312 AN: 1112006

Other (OTH) AF: 0.0176 AC: 1064 AN: 60396

GnomAD4 genome AF: 0.0312 AC: 4750 AN: 152204 Hom.: 176 Cov.: 32 AF XY: 0.0308 AC XY: 2290 AN XY: 74428

African (AFR) AF: 0.0799 AC: 3318 AN: 41524

American (AMR) AF: 0.0137 AC: 210 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.0876 AC: 454 AN: 5180

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4818

European-Finnish (FIN) AF: 0.0163 AC: 173 AN: 10594

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00745 AC: 507 AN: 68014

Other (OTH) AF: 0.0256 AC: 54 AN: 2112

Alfa AF: 0.0188 Hom.: 42

Bravo AF: 0.0351

Asia WGS AF: 0.0330 AC: 116 AN: 3478

EpiCase AF: 0.00703

EpiControl AF: 0.00848

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.52
PhyloP100		-1.2
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3746876; hg19: chr21-39671447; COSMIC: COSV107408616; COSMIC: COSV107408616;